ARV-471 is currently in Phase 2 studies for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer


Entrance to Pfizer World Headquarters in Manhattan, New York. (Credit: Coolcaesar/Wikipedia.)

Pfizer has teamed up with Arvinas to co-develop and co-commercialise ARV-471, the latter’s investigational oral PROTAC oestrogen receptor protein degrader.

ARV-471 is currently in a Phase 2 study for the treatment of oestrogen receptor (ER) positive or human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) metastatic breast cancer.

Under the agreement, Pfizer will pay $650m as an upfront payment and make a $350m equity investment in Arvinas, in exchange for a 7% equity ownership stake.

Arvinas is eligible to receive milestone payments of up to $400m in approval milestones and up to $1bn in commercial milestones.

Both parties have agreed to equally share the global development costs, commercialisation expenses and profits on ARV-471.

Pfizer oncology research and development chief scientific officer Jeff Settleman said: “We are excited to work with Arvinas to maximise ARV-471, the first PROTAC for breast cancer with encouraging early clinical data and a potential novel hormonal therapy backbone for HR+ breast cancer.

“This partnership complements Pfizer’s robust research activities in breast cancer, including our multiple next-generation CDK inhibitors currently in early clinical development.”

Arvinas is a biopharmaceutical company focused on the discovery, development and commercialisation of therapies that degrade disease-causing proteins.

The company leverages its PROTAC (proteolysis targeting chimera) Discovery Engine platform to engineer proteolysis targeting chimeras, or targeted protein degraders.

PROTAC degraders work by harnessing the body’s own natural protein disposal system to specifically degrade and remove disease-causing proteins.

ER is the primary driver of hormone receptor (HR) positive breast cancer, and endocrine therapy is used as a standard of care for ER+ breast cancer treatment.

Interim data from the ongoing Phase 1 dose escalation clinical trial underlined the potential of ARV-471 as a novel oral ER targeted therapy for metastatic ER+/HER2- breast cancer.

ARV-471 is currently in a Phase 1 dose escalation study, a Phase 1b combination study with Pfizer’s IBRANCE, and a Phase 2 monotherapy dose expansion study (VERITAC).

Furthermore, the partnership intends to conduct two additional trials of ARV-471 this year, with plans to begin Phase 3 studies in combinations with IBRANCE in 2022.

Arvinas CEO John Houston said: “This collaboration has the potential to be transformational, as it combines our leadership in targeted protein degradation with Pfizer’s global capabilities and deep expertise in breast cancer.

“This should significantly enhance and accelerate the development and potential commercialisation of ARV-471 while also advancing Arvinas’ strategy of building a global, integrated biopharmaceutical company.

“We share Pfizer’s deep commitment to people with breast cancer and are thrilled to partner with them to develop this potentially best-in-class therapy.

“Despite advancements in oncology in recent years, considerable unmet need persists in the treatment of HR+ breast cancer. Together with Pfizer, we will deploy our PROTAC technology in an effort to help people with this devastating disease.”